12-31322571-G-A

Variant names:

• chr12-31322571-G-A
• rs1844986
• NM_001135812.2:c.-21+3453C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135812.2(SINHCAF):​c.-21+3453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,412 control chromosomes in the GnomAD database, including 2,216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2216 hom., cov: 32)
• Consequence: SINHCAF NM_001135812.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135812.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SINHCAF	NM_001135812.2	MANE Select	c.-21+3453C>T		intron	N/A	NP_001129284.1
	SINHCAF	NM_001135811.2		c.-163+3453C>T		intron	N/A	NP_001129283.1
	SINHCAF	NM_021238.3		c.-159+3453C>T		intron	N/A	NP_067061.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SINHCAF	ENST00000337682.9	TSL:1 MANE Select	c.-21+3453C>T		intron	N/A	ENSP00000337477.4
	SINHCAF	ENST00000539409.5	TSL:1	c.-90+3453C>T		intron	N/A	ENSP00000443697.1
	SINHCAF	ENST00000454658.6	TSL:2	c.-21+1373C>T		intron	N/A	ENSP00000393279.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22400 AN: 151294 Hom.: 2218 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0722

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22393 AN: 151412 Hom.: 2216 Cov.: 32 AF XY: 0.144 AC XY: 10659 AN XY: 73950

African (AFR) AF: 0.0450 AC: 1860 AN: 41308

American (AMR) AF: 0.110 AC: 1675 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0722 AC: 250 AN: 3464

East Asian (EAS) AF: 0.00234 AC: 12 AN: 5126

South Asian (SAS) AF: 0.0539 AC: 259 AN: 4804

European-Finnish (FIN) AF: 0.247 AC: 2570 AN: 10418

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15130 AN: 67792

Other (OTH) AF: 0.134 AC: 281 AN: 2100

Alfa AF: 0.127 Hom.: 296

Bravo AF: 0.136

Asia WGS AF: 0.0230 AC: 78 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.83
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs1844986; hg19: chr12-31475505;