6-31764293-A-G

Variant names:

• chr6-31764293-A-G
• NM_001039651.2:c.379A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039651.2(SAPCD1):​c.379A>G​(p.Ser127Gly) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04856935).
• BP6: Variant 6-31764293-A-G is Benign according to our data. Variant chr6-31764293-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2534089.Status of the report is criteria_provided_single_submitter, 1 stars.

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.379A>G	p.Ser127Gly	missense	Exon 4 of 5	NP_001034740.1	Q5SSQ6-2
	MSH5-SAPCD1	NR_037846.1		n.3586A>G		non_coding_transcript_exon	Exon 28 of 29
	SAPCD1-AS1	NR_126423.1		n.478T>C		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.379A>G	p.Ser127Gly	missense	Exon 4 of 5	ENSP00000411948.2	Q5SSQ6-2
	MSH5-SAPCD1	ENST00000493662.6	TSL:1	n.*902A>G		non_coding_transcript_exon	Exon 28 of 29	ENSP00000417871.2
	MSH5-SAPCD1	ENST00000498473.6	TSL:1	n.*946A>G		non_coding_transcript_exon	Exon 13 of 14	ENSP00000419220.2	H0YF11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.076
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.7
DANN	Benign	0.69
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0087	N
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.16
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.028
Sift	Benign	0.37	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.17		Loss of phosphorylation at S127 (P = 0.0508)
MVP		0.030
MPC		0.19
ClinPred		0.041	T
GERP RS		-3.2
gMVP		0.059
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

hg19: chr6-31732070;