8-11444290-G-C

Position:

• chr8-11444290-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_053279.3(FAM167A):​c.122C>G​(p.Thr41Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: FAM167A NM_053279.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.19

Genes affected

FAM167A (HGNC:15549): (family with sequence similarity 167 member A)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM167A	NM_053279.3	c.122C>G	p.Thr41Ser	missense_variant	2/3	ENST00000284486.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM167A	ENST00000284486.9	c.122C>G	p.Thr41Ser	missense_variant	2/3	1	NM_053279.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 82

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.122C>G (p.T41S) alteration is located in exon 2 (coding exon 1) of the FAM167A gene. This alteration results from a C to G substitution at nucleotide position 122, causing the threonine (T) at amino acid position 41 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;.;D;T;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.5	D;D;D;.;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;.;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.90
MutPred		0.37		Gain of glycosylation at P44 (P = 0.1295);Gain of glycosylation at P44 (P = 0.1295);Gain of glycosylation at P44 (P = 0.1295);Gain of glycosylation at P44 (P = 0.1295);Gain of glycosylation at P44 (P = 0.1295);
MVP		0.16
MPC		0.041
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.75
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs1432961764; hg19: chr8-11301799;