chr17-82322294-G-C

Variant names:

• chr17-82322294-G-C
• NM_003004.3:c.614C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003004.3(SECTM1):​c.614C>G​(p.Ala205Gly) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.22

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060738236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECTM1	NM_003004.3	c.614C>G	p.Ala205Gly	missense_variant	Exon 5 of 5	ENST00000269389.8	NP_002995.1
SECTM1	XM_005256392.4	c.614C>G	p.Ala205Gly	missense_variant	Exon 5 of 5		XP_005256449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SECTM1	ENST00000269389.8	c.614C>G	p.Ala205Gly	missense_variant	Exon 5 of 5	1	NM_003004.3	ENSP00000269389.3
SECTM1	ENST00000580437	c.*58C>G		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000463904.1
SECTM1	ENST00000581864.5	n.*375C>G		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000464111.1
SECTM1	ENST00000581864.5	n.*375C>G		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000464111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614C>G (p.A205G) alteration is located in exon 5 (coding exon 4) of the SECTM1 gene. This alteration results from a C to G substitution at nucleotide position 614, causing the alanine (A) at amino acid position 205 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.0
DANN	Benign	0.33
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.036
Sift	Benign	0.28	T
Sift4G	Benign	0.59	T
Polyphen		0.67	P
Vest4		0.029
MutPred		0.20		Gain of loop (P = 0.0079);
MVP		0.055
MPC		0.17
ClinPred		0.11	T
GERP RS		-0.51
Varity_R		0.034
gMVP		0.032

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80280170;