6-31763545-C-A

Variant names:

• chr6-31763545-C-A
• rs777397695
• NM_001039651.2:c.245C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039651.2(SAPCD1):​c.245C>A​(p.Ala82Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25765446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD1	NM_001039651.2	c.245C>A	p.Ala82Asp	missense_variant	Exon 2 of 5	ENST00000415669.4	NP_001034740.1
MSH5-SAPCD1	NR_037846.1	n.3452C>A		non_coding_transcript_exon_variant	Exon 26 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAPCD1	ENST00000415669.4	c.245C>A	p.Ala82Asp	missense_variant	Exon 2 of 5	1	NM_001039651.2	ENSP00000411948.2
MSH5-SAPCD1	ENST00000493662.6	n.*768C>A		non_coding_transcript_exon_variant	Exon 26 of 29	1		ENSP00000417871.2
MSH5-SAPCD1	ENST00000493662.6	n.*768C>A		3_prime_UTR_variant	Exon 26 of 29	1		ENSP00000417871.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000411 AC: 1 AN: 243298 Hom.: 0 AF XY: 0.00000754 AC XY: 1 AN XY: 132562

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458496 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 725470

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000848 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245C>A (p.A82D) alteration is located in exon 2 (coding exon 2) of the SAPCD1 gene. This alteration results from a C to A substitution at nucleotide position 245, causing the alanine (A) at amino acid position 82 to be replaced by an aspartic acid (D). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.16	T
PROVEAN	Benign	-0.57	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.065	T;T;T
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.98	.;.;D
Vest4		0.38, 0.44
MutPred		0.28		Gain of disorder (P = 0.0614);Gain of disorder (P = 0.0614);Gain of disorder (P = 0.0614);
MVP		0.45
MPC		0.97
ClinPred		0.71	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs777397695; hg19: chr6-31731322;