6-118980207-G-T

Position:

• chr6-118980207-G-T

Variant summary

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

The ENST00000338891.12(FAM184A):​c.2232C>A​(p.His744Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: FAM184A ENST00000338891.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.281

Genes affected

FAM184A (HGNC:20991): (family with sequence similarity 184 member A) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.029585123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184A	NM_024581.6	c.2232C>A	p.His744Gln	missense_variant	10/18	ENST00000338891.12	NP_078857.5
LOC124901389	XR_007059729.1	n.76+45217G>T		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3	c.1872C>A	p.His624Gln	missense_variant	10/17		NP_001093881.1
FAM184A	NM_001288576.2	c.1872C>A	p.His624Gln	missense_variant	10/16		NP_001275505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12	c.2232C>A	p.His744Gln	missense_variant	10/18	1	NM_024581.6	ENSP00000342604	P1
	ENST00000518570.2	n.222-26276G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 06, 2021

The c.2232C>A (p.H744Q) alteration is located in exon 10 (coding exon 10) of the FAM184A gene. This alteration results from a C to A substitution at nucleotide position 2232, causing the histidine (H) at amino acid position 744 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.049
DANN	Benign	0.81
DEOGEN2	Benign	0.0063	T;T;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.030	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.57	.;N;.;.;N
MutationTaster	Benign	0.75	N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.080	.;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.38	.;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;.;.;B
Vest4		0.20
MutPred		0.039		.;Gain of methylation at K748 (P = 0.1065);.;.;Gain of methylation at K748 (P = 0.1065);
MVP		0.16
MPC		0.15
ClinPred		0.095	T
GERP RS		-10
Varity_R		0.050
gMVP		0.074

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: chr6-119301372;