NM_001039651.2:c.347A>C

Variant names:

• chr6-31764155-A-C
• rs747160705
• NM_001039651.2:c.347A>C

Variant summary

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

The NM_001039651.2(SAPCD1):​c.347A>C​(p.Glu116Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E116V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SAPCD1 NM_001039651.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033240676).

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.347A>C	p.Glu116Ala	missense	Exon 3 of 5	NP_001034740.1	Q5SSQ6-2
	MSH5-SAPCD1	NR_037846.1		n.3554A>C		non_coding_transcript_exon	Exon 27 of 29
	SAPCD1-AS1	NR_126423.1		n.616T>G		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.347A>C	p.Glu116Ala	missense	Exon 3 of 5	ENSP00000411948.2	Q5SSQ6-2
	MSH5-SAPCD1	ENST00000493662.6	TSL:1	n.*870A>C		non_coding_transcript_exon	Exon 27 of 29	ENSP00000417871.2
	MSH5-SAPCD1	ENST00000498473.6	TSL:1	n.*914A>C		non_coding_transcript_exon	Exon 12 of 14	ENSP00000419220.2	H0YF11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251452 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460686 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110912

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.076
PROVEAN	Benign	0.17	N
REVEL	Benign	0.029
Sift	Benign	0.21	T
Sift4G	Benign	0.36	T
Polyphen		0.026	B
Vest4		0.21
MutPred		0.18		Loss of ubiquitination at K117 (P = 0.0369)
MVP		0.014
MPC		0.24
ClinPred		0.023	T
GERP RS		-2.9
Varity_R		0.040
gMVP		0.099
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs747160705; hg19: chr6-31731932;