Genetic Variant NM_144635.5:c.98A>T (chr3-184338396-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144635.5(FAM131A):c.98A>T(p.Asp33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,447,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Publications

0 publications found

Variant links:

Genes affected

FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

FAM131A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19861662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144635.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM131A	NM_144635.5	MANE Select	c.98A>T	p.Asp33Val	missense	Exon 2 of 6	NP_653236.3
FAM131A	NM_001366134.1		c.-158A>T		5_prime_UTR	Exon 3 of 7	NP_001353063.1	Q6UXB0-2
FAM131A	NM_001171093.2		c.-25+1025A>T		intron	N/A	NP_001164564.1	Q6UXB0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM131A	ENST00000383847.7	TSL:2 MANE Select	c.98A>T	p.Asp33Val	missense	Exon 2 of 6	ENSP00000373360.2	Q6UXB0-3
FAM131A	ENST00000340957.9	TSL:1	c.-25+1025A>T		intron	N/A	ENSP00000340974.5	Q6UXB0-2
FAM131A	ENST00000855138.1		c.98A>T	p.Asp33Val	missense	Exon 4 of 8	ENSP00000525197.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

73266

AF XY:

0.0000532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000636

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1295434

Hom.:

Cov.:

AF XY:

0.0000650

AC XY:

AN XY:

630464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28084

American (AMR)

AF:

0.00

AC:

AN:

22006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19854

East Asian (EAS)

AF:

0.00

AC:

AN:

33500

South Asian (SAS)

AF:

0.00

AC:

AN:

65384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.0000715

AC:

AN:

1035150

Other (OTH)

AF:

0.0000557

AC:

AN:

53854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000592

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41330

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000142

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.31

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

0.044

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

M_CAP

Benign

0.037

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

PhyloP100

2.5

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.2

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Uncertain

0.0060

Vest4

0.63

MutPred

0.34

Gain of MoRF binding (P = 0.0245)

MVP

0.28

MPC

0.58

ClinPred

0.21

GERP RS

4.3

PromoterAI

0.016

Neutral

(source)

Varity_R

0.12

gMVP

0.46

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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