Genetic Variant NM_017911.4:c.512A>C (chr22-45328053-A-C) – 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_017911.4(FAM118A):c.512A>C(p.Asp171Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D171V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM118A
NM_017911.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Publications

0 publications found

Variant links:

Genes affected

FAM118A (HGNC:1313): (family with sequence similarity 118 member A) Enables identical protein binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM118A links:

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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=0.2441397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM118A	NM_017911.4	MANE Select	c.512A>C	p.Asp171Ala	missense	Exon 4 of 9	NP_060381.2	Q9NWS6-1
FAM118A	NM_001349916.2		c.554A>C	p.Asp185Ala	missense	Exon 6 of 11	NP_001336845.1
FAM118A	NM_001349914.2		c.515A>C	p.Asp172Ala	missense	Exon 4 of 9	NP_001336843.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM118A	ENST00000441876.7	TSL:1 MANE Select	c.512A>C	p.Asp171Ala	missense	Exon 4 of 9	ENSP00000395892.2	Q9NWS6-1
FAM118A	ENST00000894424.1		c.515A>C	p.Asp172Ala	missense	Exon 5 of 10	ENSP00000564483.1
FAM118A	ENST00000894426.1		c.515A>C	p.Asp172Ala	missense	Exon 4 of 9	ENSP00000564485.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1182866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

594658

African (AFR)

AF:

0.00

AC:

AN:

21634

American (AMR)

AF:

0.00

AC:

AN:

36618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23486

East Asian (EAS)

AF:

0.00

AC:

AN:

35036

South Asian (SAS)

AF:

0.00

AC:

AN:

73418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5110

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

888056

Other (OTH)

AF:

0.00

AC:

AN:

50026

GnomAD4 genome

Cov.:

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

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

0.029

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.86

M_CAP

Benign

0.012

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

PhyloP100

6.9

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.38

Vest4

0.49

MutPred

0.41

Gain of MoRF binding (P = 0.0183)

MVP

0.61

MPC

0.25

ClinPred

0.99

GERP RS

5.0

Varity_R

0.52

gMVP

0.67

Mutation Taster

=25/75

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over