chr8-11424438-T-C

Position:

• chr8-11424438-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053279.3(FAM167A):​c.580A>G​(p.Thr194Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM167A NM_053279.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

Genes affected

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

FAM167A-AS1 (HGNC:15548): (FAM167A antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05311954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM167A	NM_053279.3	c.580A>G	p.Thr194Ala	missense_variant	3/3	ENST00000284486.9
FAM167A-AS1	NR_026814.1	n.341-9482T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM167A	ENST00000284486.9	c.580A>G	p.Thr194Ala	missense_variant	3/3	1	NM_053279.3	P1
FAM167A-AS1	ENST00000533578.4	n.341-9482T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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

Apr 07, 2023

The c.580A>G (p.T194A) alteration is located in exon 3 (coding exon 2) of the FAM167A gene. This alteration results from a A to G substitution at nucleotide position 580, causing the threonine (T) at amino acid position 194 to be replaced by an alanine (A). 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	Benign	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.56
DEOGEN2	Benign	0.016	T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.61	.;.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	0.90	N;N;N;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.041
MutPred		0.18		Gain of ubiquitination at K197 (P = 0.0688);Gain of ubiquitination at K197 (P = 0.0688);Gain of ubiquitination at K197 (P = 0.0688);
MVP		0.048
MPC		0.0077
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.049
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-11281947;