rs201238305

Variant names:

• chr4-146707504-G-A
• rs201238305
• NM_031956.4:c.1378C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-146707504-G-A
• chr4-146707504-G-C
• chr4-146707504-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031956.4(TTC29):​c.1378C>T​(p.Arg460Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,609,940 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 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TTC29 NM_031956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.31
• Publications: 2 publications found

Genes affected

TTC29 (HGNC:29936): (tetratricopeptide repeat domain 29) Involved in cilium movement and cilium organization. Located in sperm flagellum. Implicated in spermatogenic failure 42. [provided by Alliance of Genome Resources, Apr 2022]

TTC29 Gene-Disease associations (from GenCC):

• spermatogenic failure 42

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015019059).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031956.4. 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
	TTC29	NM_031956.4	MANE Select	c.1378C>T	p.Arg460Cys	missense	Exon 12 of 13	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.1456C>T	p.Arg486Cys	missense	Exon 13 of 14	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.1375C>T	p.Arg459Cys	missense	Exon 12 of 13	NP_001304735.1	E7EQ14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC29	ENST00000325106.9	TSL:1 MANE Select	c.1378C>T	p.Arg460Cys	missense	Exon 12 of 13	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000508306.5	TSL:1	n.*440C>T		non_coding_transcript_exon	Exon 13 of 14	ENSP00000422648.1	E7EQZ6
	TTC29	ENST00000508306.5	TSL:1	n.*440C>T		3_prime_UTR	Exon 13 of 14	ENSP00000422648.1	E7EQZ6

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151866 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000255 AC: 63 AN: 246954 AF XY: 0.000216

Gnomad AFR exome AF: 0.000454

Gnomad AMR exome AF: 0.000350

Gnomad ASJ exome AF: 0.000599

Gnomad EAS exome AF: 0.000951

Gnomad FIN exome AF: 0.0000486

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1457956 Hom.: 0 Cov.: 29 AF XY: 0.000116 AC XY: 84 AN XY: 725322

African (AFR) AF: 0.00108 AC: 36 AN: 33378

American (AMR) AF: 0.000314 AC: 14 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.000499 AC: 13 AN: 26054

East Asian (EAS) AF: 0.000480 AC: 19 AN: 39604

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86010

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51902

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1110532

Other (OTH) AF: 0.000266 AC: 16 AN: 60210

GnomAD4 genome AF: 0.000316 AC: 48 AN: 151984 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74266

African (AFR) AF: 0.000795 AC: 33 AN: 41494

American (AMR) AF: 0.000263 AC: 4 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67942

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.000382

ESP6500AA AF: 0.000826 AC: 3

ESP6500EA AF: 0.000491 AC: 4

ExAC AF: 0.000257 AC: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3474

EpiCase AF: 0.0000547

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

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	0.081
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.1
DANN	Benign	0.82
DEOGEN2	Benign	0.00012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.047
Sift	Benign	0.064	T
Sift4G	Benign	0.099	T
Polyphen		0.0	B
Vest4		0.098
MVP		0.11
MPC		0.016
ClinPred		0.0047	T
GERP RS		-3.9
Varity_R		0.095
gMVP		0.089
Mutation Taster		=97/3	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: rs201238305; hg19: chr4-147628656; COSMIC: COSV57285327;