7-102761319-C-T

Variant names:

• chr7-102761319-C-T
• rs770103710
• NM_001145268.2:c.701C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001145268.2(FAM185A):​c.701C>T​(p.Thr234Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,394,792 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. T234N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.701C>T	p.Thr234Ile	missense_variant	Exon 4 of 8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.701C>T	p.Thr234Ile	missense_variant	Exon 4 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000656 AC: 1 AN: 152336 AF XY: 0.0000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1394792 Hom.: 0 Cov.: 30 AF XY: 0.00000291 AC XY: 2 AN XY: 687732

African (AFR) AF: 0.00 AC: 0 AN: 31214

American (AMR) AF: 0.00 AC: 0 AN: 34962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.00 AC: 0 AN: 35256

South Asian (SAS) AF: 0.0000255 AC: 2 AN: 78316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076900

Other (OTH) AF: 0.00 AC: 0 AN: 57928

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000397 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.9	.;M
PhyloP100		5.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.99	D;P
Vest4		0.74
MutPred		0.72		.;Gain of sheet (P = 0.0149);
MVP		0.22
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.76
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs770103710; hg19: chr7-102401766;