rs746280731

Variant names:

• chr17-82324759-C-G
• rs746280731
• NM_003004.3:c.226G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-82324759-C-G
• chr17-82324759-C-T

Variant summary

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

The NM_003004.3(SECTM1):​c.226G>C​(p.Ala76Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A76T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

SECTM1 (HGNC:10707): (secreted and transmembrane 1) This gene encodes a transmembrane and secreted protein with characteristics of a type 1a transmembrane protein. It is found in a perinuclear Golgi-like pattern and thought to be involved in hematopoietic and/or immune system processes. [provided by RefSeq, Jul 2008]

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=0.054701895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003004.3. 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
	SECTM1	NM_003004.3	MANE Select	c.226G>C	p.Ala76Pro	missense	Exon 3 of 5	NP_002995.1	Q8WVN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SECTM1	ENST00000269389.8	TSL:1 MANE Select	c.226G>C	p.Ala76Pro	missense	Exon 3 of 5	ENSP00000269389.3	Q8WVN6
	SECTM1	ENST00000856789.1		c.226G>C	p.Ala76Pro	missense	Exon 3 of 5	ENSP00000526848.1
	SECTM1	ENST00000856793.1		c.226G>C	p.Ala76Pro	missense	Exon 4 of 6	ENSP00000526852.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461840 Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.16
DANN	Benign	0.54
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.27
Sift	Benign	0.11	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.28		Gain of loop (P = 0.0312)
MVP		0.072
MPC		0.20
ClinPred		0.036	T
GERP RS		-5.9
Varity_R		0.075
gMVP		0.23
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs746280731; hg19: chr17-80282635;