7-102751769-G-C

Variant names:

• chr7-102751769-G-C
• rs1320821846
• NM_001145268.2:c.529G>C

Variant summary

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

The NM_001145268.2(FAM185A):​c.529G>C​(p.Glu177Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

Genes affected

FAM185A (HGNC:22412): (family with sequence similarity 185 member A)

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=0.22731325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.529G>C	p.Glu177Gln	missense_variant	Exon 2 of 8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.529G>C	p.Glu177Gln	missense_variant	Exon 2 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399166 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690082

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000344

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.529G>C (p.E177Q) alteration is located in exon 2 (coding exon 2) of the FAM185A gene. This alteration results from a G to C substitution at nucleotide position 529, causing the glutamic acid (E) at amino acid position 177 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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.097
Sift	Benign	0.14	T;D
Sift4G	Benign	0.27	T;D
Polyphen		0.98	.;D
Vest4		0.13
MutPred		0.27		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.14
ClinPred		0.74	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.49

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: rs1320821846; hg19: chr7-102392216;