Genetic Variant NM_018144.4:c.985G>T (chr10-12160939-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018144.4(SEC61A2):c.985G>T(p.Gly329Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G329R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEC61A2
NM_018144.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.82

Publications

0 publications found

Variant links:

Genes affected

SEC61A2 (HGNC:17702): (SEC61 translocon subunit alpha 2) The protein encoded by this gene has similarity to a mouse protein which suggests a role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. It may also be required for the assembly of membrane and secretory proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

SEC61A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26609483).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC61A2	NM_018144.4	MANE Select	c.985G>T	p.Gly329Trp	missense	Exon 10 of 12	NP_060614.2
SEC61A2	NM_001142628.1		c.919G>T	p.Gly307Trp	missense	Exon 9 of 11	NP_001136100.1	Q9H9S3-3
SEC61A2	NM_001142627.3		c.985G>T	p.Gly329Trp	missense	Exon 10 of 12	NP_001136099.1	Q9H9S3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC61A2	ENST00000298428.14	TSL:1 MANE Select	c.985G>T	p.Gly329Trp	missense	Exon 10 of 12	ENSP00000298428.9	Q9H9S3-1
SEC61A2	ENST00000475268.5	TSL:1	n.985G>T		non_coding_transcript_exon	Exon 10 of 13	ENSP00000436749.1	Q8TC24
SEC61A2	ENST00000379033.7	TSL:2	c.919G>T	p.Gly307Trp	missense	Exon 9 of 11	ENSP00000368319.3	Q9H9S3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460012

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111232

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0084

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.70

MutationAssessor

Benign

2.0

PhyloP100

3.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.88

REVEL

Benign

0.10

Sift

Benign

0.041

Sift4G

Benign

0.14

Polyphen

0.60

Vest4

0.61

MutPred

0.45

Loss of disorder (P = 0.0023)

MVP

0.068

MPC

1.9

ClinPred

0.82

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.90

Mutation Taster

=56/44

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over