NM_001145268.2:c.175C>T

Variant names:

• chr7-102749382-C-T
• rs766444513
• NM_001145268.2:c.175C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145268.2(FAM185A):​c.175C>T​(p.Pro59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,548,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.136
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06532422).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145268.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM185A	NM_001145268.2	MANE Select	c.175C>T	p.Pro59Ser	missense	Exon 1 of 8	NP_001138740.2	Q8N0U4-1
	FAM185A	NM_001350987.2		c.175C>T	p.Pro59Ser	missense	Exon 1 of 7	NP_001337916.2
	FAM185A	NM_001145269.2		c.175C>T	p.Pro59Ser	missense	Exon 1 of 7	NP_001138741.2	Q8N0U4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM185A	ENST00000413034.3	TSL:5 MANE Select	c.175C>T	p.Pro59Ser	missense	Exon 1 of 8	ENSP00000395340.2	Q8N0U4-1
	FAM185A	ENST00000950232.1		c.175C>T	p.Pro59Ser	missense	Exon 1 of 7	ENSP00000620291.1
	FAM185A	ENST00000880455.1		c.175C>T	p.Pro59Ser	missense	Exon 1 of 7	ENSP00000550514.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000402 AC: 6 AN: 149200 AF XY: 0.0000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000634

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000215 AC: 30 AN: 1396172 Hom.: 0 Cov.: 30 AF XY: 0.0000189 AC XY: 13 AN XY: 688618

African (AFR) AF: 0.00 AC: 0 AN: 31522

American (AMR) AF: 0.0000280 AC: 1 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25152

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79118

European-Finnish (FIN) AF: 0.0000620 AC: 3 AN: 48376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4238

European-Non Finnish (NFE) AF: 0.0000195 AC: 21 AN: 1078556

Other (OTH) AF: 0.0000346 AC: 2 AN: 57804

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000476 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.7
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.14
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.16
Sift	Benign	0.082	T
Sift4G	Benign	0.075	T
Polyphen		0.0070	B
Vest4		0.062
MutPred		0.16		Gain of phosphorylation at P59 (P = 0.011)
MVP		0.072
ClinPred		0.054	T
GERP RS		0.94
PromoterAI		-0.010	Neutral
Varity_R		0.023
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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: rs766444513; hg19: chr7-102389829;