6-31764104-C-T

Variant names:

• chr6-31764104-C-T
• rs6905572
• NM_001039651.2:c.296C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039651.2(SAPCD1):​c.296C>T​(p.Pro99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,612,636 control chromosomes in the GnomAD database, including 15,636 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1690 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13946 hom.)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.542
• Publications: 43 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003011614).
• BP6: Variant 6-31764104-C-T is Benign according to our data. Variant chr6-31764104-C-T is described in ClinVar as Benign. ClinVar VariationId is 403113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD1	NM_001039651.2	c.296C>T	p.Pro99Leu	missense_variant	Exon 3 of 5	ENST00000415669.4	NP_001034740.1
MSH5-SAPCD1	NR_037846.1	n.3503C>T		non_coding_transcript_exon_variant	Exon 27 of 29
SAPCD1-AS1	NR_126423.1	n.*31G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAPCD1	ENST00000415669.4	c.296C>T	p.Pro99Leu	missense_variant	Exon 3 of 5	1	NM_001039651.2	ENSP00000411948.2
MSH5-SAPCD1	ENST00000493662.6	n.*819C>T		non_coding_transcript_exon_variant	Exon 27 of 29	1		ENSP00000417871.2
MSH5-SAPCD1	ENST00000493662.6	n.*819C>T		3_prime_UTR_variant	Exon 27 of 29	1		ENSP00000417871.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20208 AN: 152020 Hom.: 1688 Cov.: 32

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.153 AC: 38396 AN: 251460 AF XY: 0.149

Gnomad AFR exome AF: 0.0832

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.0404

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.128 AC: 186521 AN: 1460498 Hom.: 13946 Cov.: 31 AF XY: 0.127 AC XY: 92382 AN XY: 726626

African (AFR) AF: 0.0723 AC: 2418 AN: 33464

American (AMR) AF: 0.225 AC: 10050 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 1091 AN: 26132

East Asian (EAS) AF: 0.205 AC: 8145 AN: 39694

South Asian (SAS) AF: 0.141 AC: 12135 AN: 86234

European-Finnish (FIN) AF: 0.308 AC: 16447 AN: 53412

Middle Eastern (MID) AF: 0.0711 AC: 410 AN: 5766

European-Non Finnish (NFE) AF: 0.116 AC: 128481 AN: 1110732

Other (OTH) AF: 0.122 AC: 7344 AN: 60354

GnomAD4 genome AF: 0.133 AC: 20230 AN: 152138 Hom.: 1690 Cov.: 32 AF XY: 0.143 AC XY: 10654 AN XY: 74368

African (AFR) AF: 0.0819 AC: 3398 AN: 41492

American (AMR) AF: 0.189 AC: 2895 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.152 AC: 787 AN: 5184

South Asian (SAS) AF: 0.147 AC: 706 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3459 AN: 10562

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8467 AN: 68010

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.120 Hom.: 5381

Bravo AF: 0.121

TwinsUK AF: 0.111 AC: 413

ALSPAC AF: 0.108 AC: 417

ESP6500AA AF: 0.0815 AC: 359

ESP6500EA AF: 0.122 AC: 1048

ExAC AF: 0.146 AC: 17771

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.13
DANN	Benign	0.85
DEOGEN2	Benign	0.0013	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0087	N
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.54
PROVEAN	Benign	2.8	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.99	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.052, 0.15
MPC		0.21
ClinPred		0.0013	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.065
Mutation Taster		=95/5	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: rs6905572; hg19: chr6-31731881; COSMIC: COSV65173926; COSMIC: COSV65173926;