Genetic Variant NM_153189.3:c.245A>G (chr7-123953815-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153189.3(SPAM1):c.245A>G(p.Asn82Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SPAM1
NM_153189.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08

Publications

0 publications found

Variant links:

Genes affected

SPAM1 (HGNC:11217): (sperm adhesion molecule 1) Hyaluronidase degrades hyaluronic acid, a major structural proteoglycan found in extracellular matrices and basement membranes. Six members of the hyaluronidase family are clustered into two tightly linked groups on chromosome 3p21.3 and 7q31.3. This gene was previously referred to as HYAL1 and HYA1 and has since been assigned the official symbol SPAM1; another family member on chromosome 3p21.3 has been assigned HYAL1. This gene encodes a GPI-anchored enzyme located on the human sperm surface and inner acrosomal membrane. This multifunctional protein is a hyaluronidase that enables sperm to penetrate through the hyaluronic acid-rich cumulus cell layer surrounding the oocyte, a receptor that plays a role in hyaluronic acid induced cell signaling, and a receptor that is involved in sperm-zona pellucida adhesion. Abnormal expression of this gene in tumors has implicated this protein in degradation of basement membranes leading to tumor invasion and metastasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

SPAM1 links:

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ACMG classification

Classification was made for transcript

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=0.053014368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153189.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAM1	NM_153189.3	MANE Select	c.245A>G	p.Asn82Ser	missense	Exon 3 of 5	NP_694859.1	Q5D1J4
SPAM1	NM_003117.5		c.245A>G	p.Asn82Ser	missense	Exon 3 of 7	NP_003108.2
SPAM1	NM_001174044.2		c.245A>G	p.Asn82Ser	missense	Exon 3 of 5	NP_001167515.1	P38567-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAM1	ENST00000682466.1	MANE Select	c.245A>G	p.Asn82Ser	missense	Exon 3 of 5	ENSP00000508393.1	P38567-1
SPAM1	ENST00000340011.9	TSL:1	c.245A>G	p.Asn82Ser	missense	Exon 3 of 7	ENSP00000345849.5	P38567-2
SPAM1	ENST00000439500.5	TSL:1	c.245A>G	p.Asn82Ser	missense	Exon 4 of 6	ENSP00000402123.1	P38567-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0070

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.20

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.52

M_CAP

Benign

0.0037

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

PhyloP100

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.39

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

0.78

Polyphen

0.0050

Vest4

0.061

MutPred

0.28

Gain of disorder (P = 0.0589)

MVP

0.20

MPC

0.091

ClinPred

0.049

GERP RS

-12

Varity_R

0.037

gMVP

0.32

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over