12-31293915-G-A

Position:

• chr12-31293915-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135812.2(SINHCAF):​c.245C>T​(p.Ala82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SINHCAF NM_001135812.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

SINHCAF (HGNC:30702): (SIN3-HDAC complex associated factor) Involved in negative regulation of cell migration. Part of Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

SINHCAF (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35405862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SINHCAF	NM_001135812.2	c.245C>T	p.Ala82Val	missense_variant	4/6	ENST00000337682.9	NP_001129284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SINHCAF	ENST00000337682.9	c.245C>T	p.Ala82Val	missense_variant	4/6	1	NM_001135812.2	ENSP00000337477.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.245C>T (p.A82V) alteration is located in exon 5 (coding exon 3) of the FAM60A gene. This alteration results from a C to T substitution at nucleotide position 245, causing the alanine (A) at amino acid position 82 to be replaced by a valine (V). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.69	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;.;.
Polyphen		0.84	P;P;.;.
Vest4		0.56
MutPred		0.28		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.17
MPC		0.93
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.54
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-31446849;