7-102749506-G-C

Variant names:

• chr7-102749506-G-C
• rs1306257164
• NM_001145268.2:c.299G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001145268.2(FAM185A):​c.299G>C​(p.Arg100Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000728 in 1,373,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R100H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.299G>C	p.Arg100Pro	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.299G>C	p.Arg100Pro	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373522 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 675454

African (AFR) AF: 0.00 AC: 0 AN: 31022

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23314

East Asian (EAS) AF: 0.00 AC: 0 AN: 35604

South Asian (SAS) AF: 0.00 AC: 0 AN: 74874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46816

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3982

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068414

Other (OTH) AF: 0.00 AC: 0 AN: 56760

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.7	.;M
PhyloP100		5.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		1.0	.;D
Vest4		0.77
MutPred		0.73		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.14
ClinPred		0.99	D
GERP RS		4.1
PromoterAI		0.10	Neutral
Varity_R		0.71
gMVP		0.92
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs1306257164; hg19: chr7-102389953;