NM_144605.5:c.726+241A>G

Variant names:

• chr16-4783221-T-C
• rs35853112
• NM_144605.5:c.726+241A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144605.5(SEPTIN12):​c.726+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 533,594 control chromosomes in the GnomAD database, including 20,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4635 hom., cov: 33)
  • Exomes 𝑓: 0.28 (15996 hom.)
• Consequence: SEPTIN12 NM_144605.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.529
• Publications: 1 publications found

Genes affected

SEPTIN12 (HGNC:26348): (septin 12) This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SEPTIN12 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 10

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-4783221-T-C is Benign according to our data. Variant chr16-4783221-T-C is described in ClinVar as [Benign]. Clinvar id is 1248832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN12	NM_144605.5	c.726+241A>G		intron_variant	Intron 7 of 9	ENST00000268231.13	NP_653206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN12	ENST00000268231.13	c.726+241A>G		intron_variant	Intron 7 of 9	1	NM_144605.5	ENSP00000268231.8

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36307 AN: 152066 Hom.: 4624 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.280 AC: 106941 AN: 381410 Hom.: 15996 AF XY: 0.290 AC XY: 58530 AN XY: 201566

African (AFR) AF: 0.168 AC: 1845 AN: 10986

American (AMR) AF: 0.297 AC: 4992 AN: 16810

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 3759 AN: 11682

East Asian (EAS) AF: 0.329 AC: 8179 AN: 24880

South Asian (SAS) AF: 0.414 AC: 18222 AN: 43980

European-Finnish (FIN) AF: 0.201 AC: 4537 AN: 22574

Middle Eastern (MID) AF: 0.292 AC: 480 AN: 1646

European-Non Finnish (NFE) AF: 0.260 AC: 58913 AN: 226966

Other (OTH) AF: 0.275 AC: 6014 AN: 21886

GnomAD4 genome AF: 0.239 AC: 36330 AN: 152184 Hom.: 4635 Cov.: 33 AF XY: 0.239 AC XY: 17751 AN XY: 74406

African (AFR) AF: 0.171 AC: 7100 AN: 41548

American (AMR) AF: 0.268 AC: 4094 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1654 AN: 5182

South Asian (SAS) AF: 0.423 AC: 2041 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10592

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17721 AN: 67990

Other (OTH) AF: 0.259 AC: 546 AN: 2112

Alfa AF: 0.234 Hom.: 549

Bravo AF: 0.241

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.8
DANN	Benign	0.84
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs35853112; hg19: chr16-4833222;