6-31764506-G-T

Variant names:

• chr6-31764506-G-T
• NM_001039651.2:c.512G>T

Variant summary

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

The NM_001039651.2(SAPCD1):​c.512G>T​(p.Gly171Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.565

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

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=0.08988038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD1	NM_001039651.2	c.512G>T	p.Gly171Val	missense_variant	Exon 5 of 5	ENST00000415669.4	NP_001034740.1
MSH5-SAPCD1	NR_037846.1	n.3719G>T		non_coding_transcript_exon_variant	Exon 29 of 29
SAPCD1-AS1	NR_126423.1	n.265C>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAPCD1	ENST00000415669.4	c.512G>T	p.Gly171Val	missense_variant	Exon 5 of 5	1	NM_001039651.2	ENSP00000411948.2
MSH5-SAPCD1	ENST00000493662.6	n.*1035G>T		non_coding_transcript_exon_variant	Exon 29 of 29	1		ENSP00000417871.2
MSH5-SAPCD1	ENST00000493662.6	n.*1035G>T		3_prime_UTR_variant	Exon 29 of 29	1		ENSP00000417871.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461280 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726924

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.512G>T (p.G171V) alteration is located in exon 5 (coding exon 5) of the SAPCD1 gene. This alteration results from a G to T substitution at nucleotide position 512, causing the glycine (G) at amino acid position 171 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	Benign	0.086
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.052	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Benign	0.047
Sift	Benign	0.16	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.82	.;P
Vest4		0.13
MutPred		0.24		.;Loss of methylation at R173 (P = 0.0848);
MVP		0.18
MPC		0.57
ClinPred		0.35	T
GERP RS		1.8
Varity_R		0.025
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr6-31732283;