1-16059883-G-A

Variant names:

• chr1-16059883-G-A
• rs764288909
• NM_182623.3:c.437C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_182623.3(FAM131C):​c.437C>T​(p.Ala146Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,207,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A146D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.44
• Publications: 0 publications found

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	NM_182623.3	MANE Select	c.437C>T	p.Ala146Val	missense	Exon 5 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.437C>T	p.Ala146Val	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.401C>T	p.Ala134Val	missense	Exon 4 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.269-279C>T		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1207892 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 594532

African (AFR) AF: 0.00 AC: 0 AN: 30430

American (AMR) AF: 0.00 AC: 0 AN: 33924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18922

East Asian (EAS) AF: 0.00 AC: 0 AN: 12894

South Asian (SAS) AF: 0.00 AC: 0 AN: 62970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3316

European-Non Finnish (NFE) AF: 0.00000208 AC: 2 AN: 962966

Other (OTH) AF: 0.00 AC: 0 AN: 45840

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.71		Loss of helix (P = 0.1299)
MVP		0.68
MPC		1.3
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.75
gMVP		0.65
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs764288909; hg19: chr1-16386378;