chr7-102749545-G-C

Variant names:

• chr7-102749545-G-C
• rs1243458087
• NM_001145268.2:c.338G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145268.2(FAM185A):​c.338G>C​(p.Arg113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,368,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R113Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08424485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.338G>C	p.Arg113Pro	missense_variant	Exon 1 of 8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.338G>C	p.Arg113Pro	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1368034 Hom.: 0 Cov.: 34 AF XY: 0.00000149 AC XY: 1 AN XY: 671920

African (AFR) AF: 0.00 AC: 0 AN: 31000

American (AMR) AF: 0.00 AC: 0 AN: 32736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22558

East Asian (EAS) AF: 0.00 AC: 0 AN: 35590

South Asian (SAS) AF: 0.00 AC: 0 AN: 73236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3946

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1065560

Other (OTH) AF: 0.00 AC: 0 AN: 56632

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.8
DANN	Benign	0.56
DEOGEN2	Benign	0.0039	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
PhyloP100		-0.70
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.22
Sift	Benign	0.14	T;T
Sift4G	Uncertain	0.024	D;T
Polyphen		0.0020	.;B
Vest4		0.11
MutPred		0.42		Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP		0.030
ClinPred		0.037	T
GERP RS		-3.3
Varity_R		0.12
gMVP		0.50
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1243458087; hg19: chr7-102389992;