6-118964704-G-A

Position:

• chr6-118964704-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024581.6(FAM184A):​c.3101C>T​(p.Ser1034Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM184A NM_024581.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

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

ENSG00000253194 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23925957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184A	NM_024581.6	c.3101C>T	p.Ser1034Leu	missense_variant	16/18	ENST00000338891.12	NP_078857.5
FAM184A	NM_001100411.3	c.2594C>T	p.Ser865Leu	missense_variant	15/17		NP_001093881.1
FAM184A	NM_001288576.2	c.2526+2131C>T		intron_variant			NP_001275505.1
LOC124901389	XR_007059729.1	n.76+29714G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12	c.3101C>T	p.Ser1034Leu	missense_variant	16/18	1	NM_024581.6	ENSP00000342604.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

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

Aug 20, 2024

The c.3101C>T (p.S1034L) alteration is located in exon 16 (coding exon 16) of the FAM184A gene. This alteration results from a C to T substitution at nucleotide position 3101, causing the serine (S) at amino acid position 1034 to be replaced by a leucine (L). 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	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;.;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	.;N;N;.;N
REVEL	Benign	0.24
Sift	Benign	0.11	.;T;T;.;T
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.091	.;B;.;.;.
Vest4		0.31
MutPred		0.23		.;Loss of disorder (P = 0.0334);.;.;.;
MVP		0.61
MPC		0.16
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-119285869;