Genetic Variant SMIM43:c.*444G>A (chr4-121761593-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001384332.1(SMIM43):c.*444G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,062 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: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SMIM43
NM_001384332.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.593

Publications

2 publications found

Variant links:

Genes affected

SMIM43 (HGNC:55077): (small integral membrane protein 43) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM43 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055107296).

BP6

Variant 4-121761593-C-T is Benign according to our data. Variant chr4-121761593-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3799197.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384332.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMIM43	NM_001384332.1	MANE Select	c.*444G>A	3_prime_UTR	Exon 5 of 6	NP_001371261.1	Q4W5P6
SMIM43	NM_001384333.1		c.*441G>A	3_prime_UTR	Exon 5 of 6	NP_001371262.1	Q4W5P6
SMIM43	NM_001384334.1		c.*578G>A	3_prime_UTR	Exon 4 of 5	NP_001371263.1	Q4W5P6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMIM43	ENST00000643802.2	MANE Select	c.*444G>A	3_prime_UTR	Exon 5 of 6	ENSP00000495721.1	Q4W5P6
SMIM43	ENST00000643663.2		c.*559G>A	3_prime_UTR	Exon 6 of 7	ENSP00000495936.2	Q4W5P6
SMIM43	ENST00000394394.5	TSL:3	n.587G>A	non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250486

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461062

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.000277

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111698

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.073

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.45

M_CAP

Benign

0.010

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.59

PrimateAI

Benign

0.31

Polyphen

0.0

MutPred

0.36

Gain of loop (P = 0.0045)

ClinPred

0.079

GERP RS

1.1

Varity_R

0.10

gMVP

0.0090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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