chr17-82324605-C-T

Variant names:

• chr17-82324605-C-T
• rs141592647
• NM_003004.3:c.380G>A

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.380G>A​(p.Arg127Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,392,838 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.74
• Publications: 1 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=0.036515564).

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.380G>A	p.Arg127Lys	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.380G>A	p.Arg127Lys	missense	Exon 3 of 5	ENSP00000269389.3	Q8WVN6
	SECTM1	ENST00000856789.1		c.380G>A	p.Arg127Lys	missense	Exon 3 of 5	ENSP00000526848.1
	SECTM1	ENST00000856793.1		c.380G>A	p.Arg127Lys	missense	Exon 4 of 6	ENSP00000526852.1

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 143410 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249770 AF XY: 0.0000148

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: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000184 AC: 23 AN: 1249428 Hom.: 0 Cov.: 36 AF XY: 0.0000210 AC XY: 13 AN XY: 618434

African (AFR) AF: 0.00 AC: 0 AN: 27246

American (AMR) AF: 0.00 AC: 0 AN: 38378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18276

East Asian (EAS) AF: 0.00 AC: 0 AN: 20370

South Asian (SAS) AF: 0.00 AC: 0 AN: 84332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35370

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4076

European-Non Finnish (NFE) AF: 0.0000226 AC: 22 AN: 975082

Other (OTH) AF: 0.00 AC: 0 AN: 46298

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 143410 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 69370

African (AFR) AF: 0.00 AC: 0 AN: 39384

American (AMR) AF: 0.00 AC: 0 AN: 13656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4386

South Asian (SAS) AF: 0.00 AC: 0 AN: 4104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000302 AC: 2 AN: 66222

Other (OTH) AF: 0.00 AC: 0 AN: 1994

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0010
DANN	Benign	0.76
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-7.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0070
Sift	Benign	0.67	T
Sift4G	Benign	0.57	T
Polyphen		0.050	B
Vest4		0.085
MVP		0.095
MPC		0.49
ClinPred		0.033	T
GERP RS		-7.0
Varity_R		0.037
gMVP		0.087
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: rs141592647; hg19: chr17-80282481;