Genetic Variant NM_018341.3:c.6+18C>T (chr6-169751681-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018341.3(ERMARD):c.6+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 1,550,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ERMARD
NM_018341.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.180

Publications

0 publications found

Variant links:

Genes affected

ERMARD (HGNC:21056): (ER membrane associated RNA degradation) The protein encoded by this gene contains 2 transmembrane domains near the C-terminus and is localized in the endoplasmic reticulum. Knockout of this gene in developing rat brain showed that it may be involved in neuronal migration. Mutations in this gene are associated with periventricular nodular heterotopia-6 (PVNH6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

ERMARD links:

DYNLT2 (HGNC:11695): (dynein light chain Tctex-type 2) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cytosol and sperm flagellum. Predicted to be extrinsic component of membrane. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DYNLT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-169751681-C-T is Benign according to our data. Variant chr6-169751681-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1991451.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 41 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERMARD	NM_018341.3	MANE Select	c.6+18C>T	intron	N/A	NP_060811.1	Q5T6L9-1
ERMARD	NM_001278531.2		c.6+18C>T	intron	N/A	NP_001265460.1	Q5T6L9-3
ERMARD	NM_001278533.2		c.6+18C>T	intron	N/A	NP_001265462.1	Q5T6L9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERMARD	ENST00000366773.8	TSL:2 MANE Select	c.6+18C>T	intron	N/A	ENSP00000355735.3	Q5T6L9-1
ERMARD	ENST00000418781.7	TSL:1	c.6+18C>T	intron	N/A	ENSP00000397661.2	Q5T6L9-2
ERMARD	ENST00000854211.1		c.6+18C>T	intron	N/A	ENSP00000524270.1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000841

AC:

AN:

154648

AF XY:

0.0000487

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.000167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000436

AC:

AN:

1397708

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

689666

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

31566

American (AMR)

AF:

0.000172

AC:

AN:

34882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24858

East Asian (EAS)

AF:

0.00

AC:

AN:

35970

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48640

Middle Eastern (MID)

AF:

0.000191

AC:

AN:

5222

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079314

Other (OTH)

AF:

0.000225

AC:

AN:

57818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000269

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000793

AC:

AN:

41590

American (AMR)

AF:

0.000523

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000359

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.85

PhyloP100

-0.18

PromoterAI

0.059

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over