17-82322249-G-T

Variant names:

• chr17-82322249-G-T
• rs138392672
• NM_003004.3:c.659C>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.659C>A​(p.Pro220Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. P220L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• 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=0.06316084).

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.659C>A	p.Pro220Gln	missense	Exon 5 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.659C>A	p.Pro220Gln	missense	Exon 5 of 5	ENSP00000269389.3	Q8WVN6
	SECTM1	ENST00000856789.1		c.659C>A	p.Pro220Gln	missense	Exon 5 of 5	ENSP00000526848.1
	SECTM1	ENST00000856793.1		c.659C>A	p.Pro220Gln	missense	Exon 6 of 6	ENSP00000526852.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455302 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722868

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 44302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107192

Other (OTH) AF: 0.0000166 AC: 1 AN: 60116

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.61
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.67	P
Vest4		0.14
MutPred		0.25		Gain of helix (P = 0.0164)
MVP		0.014
MPC		0.16
ClinPred		0.083	T
GERP RS		-1.6
Varity_R		0.053
gMVP		0.075

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: rs138392672; hg19: chr17-80280125;