1-16059916-T-A

Variant names:

• chr1-16059916-T-A
• rs377599440
• NM_182623.3:c.404A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182623.3(FAM131C):​c.404A>T​(p.His135Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,363,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. H135R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07444075).

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.404A>T	p.His135Leu	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.404A>T	p.His135Leu	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.368A>T	p.His123Leu	missense	Exon 4 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.269-312A>T		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247218 AF XY: 0.00

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: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1363348 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 676998

African (AFR) AF: 0.00 AC: 0 AN: 32250

American (AMR) AF: 0.00 AC: 0 AN: 39058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23270

East Asian (EAS) AF: 0.00 AC: 0 AN: 27318

South Asian (SAS) AF: 0.00 AC: 0 AN: 78756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1055666

Other (OTH) AF: 0.00 AC: 0 AN: 54668

GnomAD4 genome Cov.: 19

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.1
DANN	Benign	0.96
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.016
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.042
Sift	Benign	0.044	D
Sift4G	Benign	0.12	T
Polyphen		0.49	P
Vest4		0.17
MutPred		0.26		Loss of disorder (P = 0.0755)
MVP		0.37
MPC		0.86
ClinPred		0.26	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.35
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs377599440; hg19: chr1-16386411;