chr6-31764523-C-T

Variant names:

• chr6-31764523-C-T
• rs777749400
• NM_001039651.2:c.529C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039651.2(SAPCD1):​c.529C>T​(p.Arg177Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000826 in 1,610,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. R177S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000084 (1 hom.)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.230
• Publications: 3 publications found

Genes affected

SAPCD1 (HGNC:13938): (suppressor APC domain containing 1)

MSH5-SAPCD1 (HGNC:41994): (MSH5-SAPCD1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring mutS homolog 5 (MSH5) and chromosome 6 open reading frame 26 (C6orf26) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

SAPCD1-AS1 (HGNC:39824): (SAPCD1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048752427).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039651.2. 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
	SAPCD1	NM_001039651.2	MANE Select	c.529C>T	p.Arg177Cys	missense	Exon 5 of 5	NP_001034740.1	Q5SSQ6-2
	MSH5-SAPCD1	NR_037846.1		n.3736C>T		non_coding_transcript_exon	Exon 29 of 29
	SAPCD1-AS1	NR_126423.1		n.248G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAPCD1	ENST00000415669.4	TSL:1 MANE Select	c.529C>T	p.Arg177Cys	missense	Exon 5 of 5	ENSP00000411948.2	Q5SSQ6-2
	MSH5-SAPCD1	ENST00000493662.6	TSL:1	n.*1052C>T		non_coding_transcript_exon	Exon 29 of 29	ENSP00000417871.2
	MSH5-SAPCD1	ENST00000498473.6	TSL:1	n.*1096C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000419220.2	H0YF11

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250442 AF XY: 0.0000591

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.0000836 AC: 122 AN: 1458710 Hom.: 1 Cov.: 31 AF XY: 0.0000772 AC XY: 56 AN XY: 725792

African (AFR) AF: 0.0000599 AC: 2 AN: 33410

American (AMR) AF: 0.0000895 AC: 4 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5058

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1110072

Other (OTH) AF: 0.000897 AC: 54 AN: 60234

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5198

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00191 AC: 4 AN: 2090

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.088	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.23
PROVEAN	Benign	0.020	N
REVEL	Benign	0.063
Sift	Benign	0.14	T
Sift4G	Uncertain	0.026	D
Polyphen		0.97	D
Vest4		0.14
MutPred		0.27		Loss of solvent accessibility (P = 0.0111)
MVP		0.24
MPC		0.58
ClinPred		0.081	T
GERP RS		1.2
Varity_R		0.078
gMVP		0.11
Mutation Taster		=94/6	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: rs777749400; hg19: chr6-31732300; COSMIC: COSV100991930; COSMIC: COSV100991930;