6-31764284-A-G

Variant names:

• chr6-31764284-A-G
• NM_001039651.2:c.370A>G

Variant summary

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

The NM_001039651.2(SAPCD1):​c.370A>G​(p.Asn124Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 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)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100

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=0.07835296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD1	NM_001039651.2	c.370A>G	p.Asn124Asp	missense_variant	Exon 4 of 5	ENST00000415669.4	NP_001034740.1
MSH5-SAPCD1	NR_037846.1	n.3577A>G		non_coding_transcript_exon_variant	Exon 28 of 29
SAPCD1-AS1	NR_126423.1	n.487T>C		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.370A>G	p.Asn124Asp	missense_variant	Exon 4 of 5	1	NM_001039651.2	ENSP00000411948.2
MSH5-SAPCD1	ENST00000493662.6	n.*893A>G		non_coding_transcript_exon_variant	Exon 28 of 29	1		ENSP00000417871.2
MSH5-SAPCD1	ENST00000493662.6	n.*893A>G		3_prime_UTR_variant	Exon 28 of 29	1		ENSP00000417871.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370A>G (p.N124D) alteration is located in exon 4 (coding exon 4) of the SAPCD1 gene. This alteration results from a A to G substitution at nucleotide position 370, causing the asparagine (N) at amino acid position 124 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
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Uncertain	0.99
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.074
Sift	Benign	0.095	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.14		Gain of phosphorylation at S127 (P = 0.098);
MVP		0.014
MPC		0.43
ClinPred		0.043	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31732061;